Lauri J. Lehto

Detection of calcifications in vivo and ex vivo after brain injury in rat using SWIFT

Calcifications represent one component of pathology in many brain diseases. With MRI, they are most often detected by exploiting negative contrast in magnitude images. Calcifications are more diamagnetic than tissue, leading to a magnetic field disturbance that can be seen in phase MR images. Most phase imaging studies use gradient recalled echo based pulse sequences. Here, the phase component of SWIFT, a virtually zero acquisition delay sequence, was used to detect calcifications ex vivo and in vivo in rat models of status epilepticus and traumatic brain injury. Calcifications were detected in phase and imaginary SWIFT images based on their dipole like magnetic field disturbances. In magnitude SWIFT images, calcifications were distinguished as hypointense and hyperintense. Hypointense calcifications showed large crystallized granules with few surrounding inflammatory cells, while hyperintense calcifications contained small granules with the presence of more inflammatory cells. The size of the calcifications in SWIFT magnitude images correlated with that in Alizarin stained histological sections. Our data indicate that SWIFT is likely to better preserve signal in the proximity of a calcification or other field perturber in comparison to gradient echo due to its short acquisition delay and broad excitation bandwidth. Furthermore, a quantitative description for the phase contrast near dipole magnetic field inhomogeneities for the SWIFT pulse sequence is given. In vivo detection of calcifications provides a tool to probe the progression of pathology in neurodegenerative diseases. In particular, it appears to provide a surrogate marker for inflammatory cells around the calcifications after brain injury.

Multimodal MRI assessment of damage and plasticity caused by status epilepticus in the rat brain

Status epilepticus or other brain‐damaging insults launch a cascade of events that may lead to the development of epilepsy. MRI techniques available today, including T2‐ and T1‐weighted imaging, functional MRI, manganese enhanced MRI (MEMRI), arterial spin labeling (ASL), diffusion tensor imaging (DTI), and phase imaging, can detect not only damage caused by status epilepticus but also plastic changes in the brain that occur in response to damage. Optimal balance between damage and recovery processes is a key for planning possible treatments, and noninvasive imaging has the potential to greatly facilitate this process and to make personalized treatment plans possible.

Osteochondral Repair: Evaluation with Sweep Imaging with Fourier Transform in an Equine Model

PURPOSE To evaluate the status of articular cartilage and bone in an equine model of spontaneous repair by using the sweep imaging with Fourier transform (SWIFT) magnetic resonance (MR) imaging technique. MATERIALS AND METHODS Experiments were approved by the Utrecht University Animal Ethics Committee. Six-millimeter-diameter chondral (n = 5) and osteochondral (n = 5, 3-4 mm deep into subchondral bone) defects were created in the intercarpal joints of seven 2-year-old horses and examined with SWIFT at 9.4 T after spontaneous healing for 12 months. Conventional T2 maps and gradient-echo images were obtained for comparison, and histologic assessment of cartilage and micro-computed tomography (CT) of bone were performed for reference. Signal-to-noise ratio (SNR) analysis was performed, and a radiologist evaluated the MR images. Structural bone parameters were derived from SWIFT and micro-CT datasets. Significance of differences was investigated with the Wilcoxon signed rank test and Pearson correlation analysis. RESULTS SWIFT was able to depict the different outcomes of spontaneous healing of focal chondral versus osteochondral defects. SWIFT produced constant signal intensity throughout cartilage, whereas T2 mapping showed elevated T2 values (P = .06) in repair tissue (mean T2 in superficial region of interest in an osteochondral lesion = 50.0 msec ± 10.2) in comparison to adjacent intact cartilage (mean T2 = 32.7 msec ± 4.2). The relative SNR in the subchondral plate with SWIFT (0.91) was more than four times higher than that with conventional fast spin-echo (0.12) and gradient-echo (0.19) MR imaging. The correlation between bone volume-to-tissue volume fractions determined with SWIFT and micro-CT was significant (r = 0.83, P < .01). CONCLUSION SWIFT enabled assessment of spontaneous osteochondral repair in an equine model.

Orientation selective deep brain stimulation

OBJECTIVE Target selectivity of deep brain stimulation (DBS) therapy is critical, as the precise locus and pattern of the stimulation dictates the degree to which desired treatment responses are achieved and adverse side effects are avoided. There is a clear clinical need to improve DBS technology beyond currently available stimulation steering and shaping approaches. We introduce orientation selective neural stimulation as a concept to increase the specificity of target selection in DBS. APPROACH This concept, which involves orienting the electric field along an axonal pathway, was tested in the corpus callosum of the rat brain by freely controlling the direction of the electric field on a plane using a three-electrode bundle, and monitoring the response of the neurons using functional magnetic resonance imaging (fMRI). Computational models were developed to further analyze axonal excitability for varied electric field orientation. MAIN RESULTS Our results demonstrated that the strongest fMRI response was observed when the electric field was oriented parallel to the axons, while almost no response was detected with the perpendicular orientation of the electric field relative to the primary fiber tract. These results were confirmed by computational models of the experimental paradigm quantifying the activation of radially distributed axons while varying the primary direction of the electric field. SIGNIFICANCE The described strategies identify a new course for selective neuromodulation paradigms in DBS based on axonal fiber orientation.

Minor Influence of Lifelong Voluntary Exercise on Composition, Structure, and Incidence of Osteoarthritis in Tibial Articular Cartilage of Mice Compared with Major Effects Caused by Growth, Maturation, and Aging

We investigated the effects of lifelong voluntary exercise on articular cartilage of mice. At the age of 4 weeks C57BL mice (n = 152) were divided into two groups, with one group serving as a sedentary control whereas the other was allowed free access to a running wheel from the age of 1 month onward. Mice were euthanized at four different time points (1, 2, 6, and 18 months of age). Articular cartilage samples were gathered from the load-bearing area of the tibial medial plateaus, and osteoarthritis was graded. Additionally, the proteoglycan content distribution was assessed using digital densitometry, collagen fibril orientation, and parallelism with polarized light microscopy, and collagen content using Fourier transform infrared imaging spectroscopy. The incidence of osteoarthritis increased with aging, but exercise had no effect on this trend. Furthermore, the structure and composition revealed significant growth, maturation, and age-dependent properties. Exercise exerted a minor effect on collagen fibril orientation in the superficial zone. Fibril orientation at 2 months of age was more perpendicular to surface (p < 0.05) in controls compared with runners, whereas the situation was reversed at the age of 18 months (p < 0.05). The collagen content of the superficial zone was higher (p < 0.01) at the age of 18 months in controls compared with runners but the proteoglycan content did not display any exercise-dependent changes. In conclusion, growth, maturation, and aging exerted a clear effect on integrity, structure, and composition of medial tibial plateau articular cartilage in mice, whereas lifelong voluntary exercise had only a minor effect on collagen architecture and content.

Measurement of T1 relaxation time of osteochondral specimens using VFA-SWIFT

To evaluate the feasibility of SWIFT with variable flip angle (VFA) for measurement of T1 relaxation time in Gd‐agarose‐phantoms and osteochondral specimens, including regions of very short T2*, and compare with T1 measured using standard methods

Magnetization transfer SWIFT MRI consistently detects histologically verified myelin loss in the thalamocortical pathway after a traumatic brain injury in rat: MT-SWIFT after TBI

Traumatic brain injury (TBI) is associated with various neurocognitive deficits, and rapid assessment of the damage is potentially important for the prevention and treatment of these deficits. Imaging assessment of mild or moderate damage outside the primary lesion area after TBI, however, remains challenging. Magnetization transfer (MT) has clearly been underutilized in imaging the damage caused by TBI. Here, we applied the MT ratio (MTR) using sweep imaging with Fourier transformation (SWIFT) to study microstructural tissue damage in the thalamocortical pathway outside the primary lesion in a lateral fluid percussion injury rat model of TBI, 5 months after injury. MTR was decreased in layers VIb‐IV of the barrel cortex and related subcortical areas, mainly indicating demyelination, which was verified by histology. The largest MTR change in the cortex was in layer VIb (−8.2%, pFDR = 0.01), and the largest MTR change in the subcortical areas was in the caudal‐most portion of the internal capsule (−11.0%, pFDR < 0.005). These areas exhibited the greatest demyelination and substantial cellularity attributed to gliosis. Correlation analysis of group‐averaged results from the subcortical areas revealed an excellent correlation of MTR with myelin (r2 = 0.94, p < 0.001), but no correlation with increased cellularity as detected by Nissl staining. Thus, MTR using SWIFT can be a valuable tool for the assessment of subtle changes after TBI in both cortical and subcortical areas.

Evoked local field potentials can explain temporal variation in blood oxygenation level-dependent responses in rat somatosensory cortex

The aim of this study was to explain the temporal variations between subjects in the blood oxygenation level‐dependent (BOLD) response. Somatosensory responses were elicited with the electrical forepaw stimulus at a frequency of 10 Hz in urethane‐anesthetized rats, and functional magnetic resonance imaging (fMRI) with BOLD contrast and local field potential (LFP) measurements were performed simultaneously. BOLD fMRI activation was evaluated by two different models, one based on the stimulus paradigm (the block model) and the other on the simultaneously measured evoked LFP responses. In the initial analysis, the LFP model captured the BOLD activation in the primary somatosensory cortex in all cases, and the block model in 10 of 12 rats. A statistical comparison of the two models revealed that the LFP‐derived model was able to explain additional BOLD variation over the block model in the somatosensory cortex in nine of 12 rats. These results suggest that there is more information regarding neuronal activity in the BOLD signal than can be exploited using the block model alone. Furthermore, the hemodynamic coupling remains unchanged in the case of temporally variable BOLD signals. Copyright

Phase imaging in brain using SWIFT.

The majority of MRI phase imaging is based on gradient recalled echo (GRE) sequences. This work studies phase contrast behavior due to small off-resonance frequency offsets in brain using SWIFT, a FID-based sequence with nearly zero acquisition delay. 1D simulations and a phantom study were conducted to describe the behavior of phase accumulation in SWIFT. Imaging experiments of known brain phase contrast properties were conducted in a perfused rat brain comparing GRE and SWIFT. Additionally, a human brain sample was imaged. It is demonstrated how SWIFT phase is orientation dependent and correlates well with GRE, linking SWIFT phase to similar off-resonance sources as GRE. The acquisition time is shown to be analogous to TE for phase accumulation time. Using experiments with and without a magnetization transfer preparation, the likely effect of myelin water pool contribution is seen as a phase increase for all acquisition times. Due to the phase accumulation during acquisition, SWIFT phase contrast can be sensitized to small frequency differences between white and gray matter using low acquisition bandwidths.

MB-SWIFT functional MRI during deep brain stimulation in rats

Abstract Recently introduced 3D radial MRI pulse sequence entitled Multi‐Band SWeep Imaging with Fourier Transformation (MB‐SWIFT) having virtually zero acquisition delay was used to obtain functional MRI (fMRI) contrast in rats brain at 9.4 T during deep brain stimulation (DBS). The results demonstrate that MB‐SWIFT allows functional images free of susceptibility artifacts, and provides an excellent fMRI activation contrast in the brain. Flip angle dependence of the MB‐SWIFT fMRI signal and elimination of the fMRI contrast while using saturation bands, indicate a blood flow origin of the observed fMRI contrast. MB‐SWIFT fMRI modality permits activation studies in the close proximity to an implanted lead, which is not possible to achieve with conventionally used gradient echo and spin echo ‐ echo planar imaging fMRI techniques. We conclude that MB‐SWIFT fMRI is a powerful imaging modality for investigations of functional responses during DBS. Graphical abstract Symbol. No caption available. HighlightsMB‐SWIFT is a virtually zero‐TE pulse sequence and it can achieve high bandwidths.It is shown to produce functional contrast during deep brain stimulation in rats.Susceptibility artefact surrounding the electrode is minimized.The extent and amplitude of the functional response are similar to that of SE‐EPI.The functional contrast is related to inflow of blood.